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橙皮苷诱导肝癌细胞中依赖半胱天冬酶8的凋亡并抑制血管内皮生长因子的产生。

Clausenidin Induces Caspase 8-Dependent Apoptosis and Suppresses Production of VEGF in Liver Cancer Cells.

作者信息

Waziri Peter M, Abdullah Rasedee, Rosli Rosita, Omar Abdul Rahman, Abdul Ahmad Bustamam, Kassim Nur Kartinee, Malami Ibrahim, Etti Imaobong C, Sani Ja’afaru M, Mohd Lila Mohd Azmi, Abdullah Jesse Faez Firdaus

机构信息

MAKNA Cancer Research Laboratory, Institute of Bioscience, University Putra Malaysia, Serdang, Selangor, Malaysia.

Department of Biochemistry, Kaduna State University, Main Campus, PMB 2336, Kaduna, Nigeria. Email:

出版信息

Asian Pac J Cancer Prev. 2018 Apr 25;19(4):917-922. doi: 10.22034/APJCP.2018.19.4.917.

DOI:10.22034/APJCP.2018.19.4.917
PMID:29693341
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6031786/
Abstract

Clausena excavata Burm f. is used by traditional healers to treat cancer patients in South East Asia. The use of the plant and its compounds is based on Asian folklore with little or no scientific evidence supporting the therapeutic efficacy The current study aimed to determine the effect of pure clausenidin isolated from C. excavata on caspase-8-induced cell death as well as angiogenesis in the HepG2 hepatocellular carcinoma cell line. Caspase-8 and extrinsic death receptor protein expression was determined using spectrophotometry and protein profile arrays, respectively. Ultrastructural analysis of clausenidin-treated cells was conducted using transmission electron microscopy. In addition, anti-angiogenic effects of clausenidin were investigated by Western blot analysis. Clausenidin significantly (p<0.05) increased the activity of caspase-8 and expression of protein components of the death inducing signaling complex (DISC) in HepG2 cells. Ultrastructural analysis of the clausenidin-treated HepG2 cells revealed morphological abnormalities typical of apoptosis. Furthermore, clausenidin significantly (p<0.05) decreased the expression of vascular endothelial growth factor (VEGF). Therefore, clausenidin is a potential anti-angiogenic agent which may induce apoptosis of hepatocellular carcinoma cells.

摘要

臭节草被东南亚的传统治疗师用于治疗癌症患者。对该植物及其化合物的使用基于亚洲民间传说，几乎没有科学证据支持其治疗效果。当前的研究旨在确定从臭节草中分离出的纯吴茱萸次碱对HepG2肝癌细胞系中半胱天冬酶 - 8诱导的细胞死亡以及血管生成的影响。分别使用分光光度法和蛋白质谱阵列测定半胱天冬酶 - 8和外源性死亡受体蛋白的表达。使用透射电子显微镜对经吴茱萸次碱处理的细胞进行超微结构分析。此外，通过蛋白质印迹分析研究吴茱萸次碱的抗血管生成作用。吴茱萸次碱显著（p<0.05）增加了HepG2细胞中半胱天冬酶 - 8的活性以及死亡诱导信号复合物（DISC）的蛋白质成分的表达。对经吴茱萸次碱处理的HepG2细胞的超微结构分析揭示了典型的凋亡形态异常。此外，吴茱萸次碱显著（p<0.05）降低了血管内皮生长因子（VEGF）的表达。因此，吴茱萸次碱是一种潜在的抗血管生成剂，可能诱导肝癌细胞凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec6d/6031786/3221a3c768ab/APJCP-19-917-g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec6d/6031786/3221a3c768ab/APJCP-19-917-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec6d/6031786/e03fea39ce85/APJCP-19-917-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec6d/6031786/3221a3c768ab/APJCP-19-917-g007.jpg

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